title: A whole-organism screen identifies new regulators of fat storage.
abstract: The regulation of energy homeostasis integrates diverse biological processes ranging from behavior to metabolism and is linked fundamentally to numerous disease states. To identify new molecules that can bypass homeostatic compensatory mechanisms of energy balance in intact animals, we screened for small-molecule modulators of Caenorhabditis elegans fat content. We report on several molecules that modulate fat storage without obvious deleterious effects on feeding, growth and reproduction. A subset of these compounds also altered fat storage in mammalian and insect cell culture. We found that one of the newly identified compounds exerts its effects in C. elegans through a pathway that requires previously undescribed functions of an AMP-activated kinase catalytic subunit and a transcription factor previously unassociated with fat regulation. Thus, our strategy identifies small molecules that are effective within the context of intact animals and reveals relationships between new pathways that operate across phyla to influence energy homeostasis.
authors.affiliation: Department of Anatomy, University of California, San Francisco, San Francisco, California, USA.
authors.forename: George A
authors.initials: GA
authors.lastname: Lemieux
authors.forename: Jason
authors.initials: J
authors.lastname: Liu
authors.forename: Nasima
authors.initials: N
authors.lastname: Mayer
authors.forename: Roland J
authors.initials: RJ
authors.lastname: Bainton
authors.forename: Kaveh
authors.initials: K
authors.lastname: Ashrafi
authors.forename: Zena
authors.initials: Z
authors.lastname: Werb
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002384:Catalysis; D004734:Energy Metabolism; D005223:Fats / Q000378:metabolism*; D006706:Homeostasis; D050356:Lipid Metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D005223:Fats; D055372:AMP-Activated Protein Kinases